Dikošová Lívia, Otočková Barbora, Malatinský Tomáš, Doháňošová Jana, Kopáčová Mária, Ďurinová Anna, Smutná Lucie, Trejtnar František, Fischer Róbert
Institute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology in Bratislava Radlinského 9 812 37 Bratislava Slovak Republic
Central Laboratories, Slovak University of Technology in Bratislava Radlinského 9 812 37 Bratislava Slovak Republic.
RSC Adv. 2021 Sep 24;11(50):31621-31630. doi: 10.1039/d1ra06225e. eCollection 2021 Sep 21.
A unique synthesis of polyhydroxylated pyrrolizidine alkaloids, namely (+)-hyacinthacine C and (+)-5--hyacinthacine C is presented. The strategy relies on a 1,3-dipolar cycloaddition of an l-mannose derived nitrone, which owing to its great -stereoselectivity builds up the majority of the required stereocenters. The following key steps include Wittig olefination and iodine-mediated aminocyclisation, that provide two epimeric pyrrolizidines with the appropriate configuration. As a result, structure and steric arrangement of the first synthetically prepared (+)-hyacinthacine C are proved to be correct, clearly confirming the inconsistency with the stereochemistry assigned to the natural sample. With respect to the previously proven glycosidase inhibitory activities, the antiproliferative effect of (+)-hyacinthacine C and (+)-5--hyacinthacine C was evaluated using several cell line models.
本文介绍了一种独特的多羟基化吡咯里西啶生物碱的合成方法，即（+）-风信子碱C和（+）-5-表风信子碱C。该策略依赖于由L-甘露糖衍生的硝酮的1,3-偶极环加成反应，由于其高度的立体选择性，构建了大部分所需的立体中心。随后的关键步骤包括维蒂希烯烃化反应和碘介导的氨基环化反应，这两个反应提供了具有适当构型的两个差向异构吡咯里西啶。结果表明，首次合成制备的（+）-风信子碱C的结构和空间排列是正确的，这清楚地证实了其与天然样品所指定的立体化学不一致。关于先前已证实的糖苷酶抑制活性，使用几种细胞系模型评估了（+）-风信子碱C和（+）-5-表风信子碱C的抗增殖作用。
